Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer


About this study

The purpose of this trial is to determine how well estradiol works in treating patients with estrogen receptor beta (ER beta) positive, triple negative breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Hormone receptors like ER beta allow the body to respond appropriately to hormones. Triple negative means that the breast cancer does not express other hormone receptors called ER alpha, progesterone, and HER2. In some people with triple negative breast cancer, ER beta is overexpressed. Tumor cells that overexpress ER beta grow slower in the laboratory and this growth is slowed in the presence of estrogen. Estradiol is a form of estrogen. This study may help doctors determine whether tumor cells that overexpress ER beta shrink in the presence of estradiol.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- PRE-SCREENING CRITERIA (STEP 0): History of locally advanced or metastatic breast
cancer that is ERalpha negative or low (< 1% nuclear staining) and HER2 negative.

- Note: HER2 negative disease per 2018 American Society of Clinical
Oncology/College of American of Pathologists (ASCO/CAP) guidelines, one of the
following must apply:

- 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ
hybridization (ISH);

- 0 or 1+ by IHC and ISH not done;

- 2+ by IHC and ISH results are: < 6.0 HER2 signals/cell with HER2/CEP17 ratio
< 2.0;

- IHC not done and not amplified by ISH.

- PRE-SCREENING CRITERIA (STEP 0): =< 3 prior chemotherapy regimens for treatment of
metastatic breast cancer.

- Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed (if
administered as monotherapy it is not counted as a chemotherapy regimen).

- PRE-SCREENING CRITERIA (STEP 0): Eastern Cooperative Oncology Group (ECOG) performance
status 0 or 1

- PRE-SCREENING CRITERIA (STEP 0): Willing to submit a biopsy specimen from locally
recurrent or metastatic site (or primary if metastatic site not available) of breast
cancer for ERbeta staining to Mayo Clinic Anatomic Pathology.

- PRE-REGISTRATION CRITERIA (STEP 1): Presence of moderate or strong nuclear ERbeta
staining in > 25% of cells in specimen submitted during Pre-Screening Step.

- PRE-REGISTRATION CRITERIA (STEP 1): For patients who did not have a biopsy or lacking
ERalpha, progesterone receptor (PR), and HER2 results from a locally advanced or
metastatic site performed =< 12 months prior to Pre-Registration: Willing to undergo a
standard of care biopsy of locally recurrent or metastatic breast cancer for ERalpha,
PR, and HER2 as well as additional research cores.

- PRE-REGISTRATION CRITERIA (STEP 1): Measurable or non-measurable disease as defined by
Response Evaluation Criteria in Solid Tumors (RECIST) criteria that will be assessed
using imaging-based evaluations.

- Note: The tumor lesion biopsied during the pre-registration period is not
considered measurable disease nor a target lesion.

- PRE-REGISTRATION CRITERIA (STEP 1): If history of brain metastases must meet the
following criteria:

- Patients with a history of brain metastases are eligible only if they are
asymptomatic and have stable disease for >= 3 months, including < 28 days of
prior to pre-registration.

- Not receiving steroids for brain metastases.

- PRE-REGISTRATION CRITERIA (STEP 1): ECOG performance status 0 or 1.

- PRE-REGISTRATION CRITERIA (STEP 1): =< 3 prior chemotherapy regimens for treatment of
metastatic breast cancer.

- NOTE: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed.

- PRE-REGISTRATION CRITERIA (STEP 1): Women must be postmenopausal.

- NOTE: Postmenopausal status is verified by:

- Prior bilateral surgical oophorectomy, or

- Age >= 60 years, or

- Age < 60 years with no menses for > 1 year with estradiol levels within
postmenopausal range, according to institutional standard.

- PRE-REGISTRATION CRITERIA (STEP 1): Able to swallow oral medications.

- PRE-REGISTRATION CRITERIA (STEP 1): Willingness to stop use of strong inducers or
inhibitors of CYP3A4 prior to registration.

- NOTE: Use of strong inducers or inhibitors is allowed during pre-registration as
long as patient will complete course prior to registration.

- REGISTRATION CRITERIA (STEP 2): For patents who had a biopsy taken from a metastatic
site =< 12 months prior to Pre-Registration: Confirmation from the local lab that the
tumor from this biopsy was ERalpha negative (< 1% nuclear staining) and HER2 negative

- REGISTRATION CRITERIA (STEP 2): For patients who underwent a pre-registration biopsy:
Histologic confirmation from local lab that tumor is ERalpha negative (< 1% nuclear
staining), and HER2 negative

- REGISTRATION CRITERIA (STEP 2): Hemoglobin >= 8 g/dL (=< 14 days prior to

- REGISTRATION CRITERIA (STEP 2): Platelet count >= 75,000/mm^3 (=< 14 days prior to

- REGISTRATION CRITERIA (STEP 2): Creatinine =< 1.5 x upper limit of normal (ULN) (=< 14
days prior to registration).

- REGISTRATION CRITERIA (STEP 2): Total bilirubin =< 1.5 x ULN (=< 14 days prior to

- REGISTRATION CRITERIA (STEP 2): Aspartate aminotransferase/serum glutamic-oxaloacetic
transaminase (AST/SGOT) =< 2.5 x ULN (=< 14 days prior to registration).

- For patients with liver metastasis =< 5 x ULN.

Exclusion Criteria:

- PRE-REGISTRATION CRITERIA: Uncontrolled intercurrent illness including, but not
limited to:

- Ongoing or active infection.

- Symptomatic congestive heart failure.

- Unstable angina pectoris.

- Uncontrolled symptomatic cardiac arrhythmia.

- Uncontrolled hypertension (defined as blood pressure > 160/90).

- PRE-REGISTRATION CRITERIA: Deep vein thrombosis / pulmonary embolism (DVT/PE) =< 12
months prior to pre-registration.

- Note: Patients who are on anticoagulant therapy for maintenance are eligible as
long as the DVT and/or PE occurred > 6 months prior to pre-registration, and
there is no evidence for active thrombosis (either DVT or PE).

- PRE-REGISTRATION CRITERIA: Stroke =< 6 months prior to pre-registration.

- PRE-REGISTRATION CRITERIA: Two or more episodes of DVT and/or PE =< 5 years prior to

- PRE-REGISTRATION CRITERIA: Abnormal uterine bleeding =< 6 months prior to

- PRE-REGISTRATION CRITERIA: History of coagulopathy.

- PRE-REGISTRATION CRITERIA: Other active second malignancy other than non-melanoma skin
cancers within 3 years prior to pre-registration.

- NOTE: A second malignancy is not considered active if all treatment for that
malignancy is completed and the patient has been disease-free for >= 3 years
prior to pre-registration.

- REGISTRATION CRITERIA: None of the following therapies are allowed =< 14 days prior to

- Chemotherapy.

- Immunotherapy.

- Biologic therapy.

- Hormonal therapy.

- Monoclonal antibodies.

- Anti-HER2 or other "targeted" (e.g. mTOR) therapy.

- Note: Any adverse events derived from these therapies must be =< grade 2 prior to
starting study therapy (exceptions for alopecia).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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